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ORIGINAL RESEARCH article

Front. Behav. Neurosci.

Sec. Individual and Social Behaviors

The nonnuclear DifB NF-κB isoform affects courtship, circadian, and locomotor behavior in adult Drosophila melanogaster

Provisionally accepted
Thilini  WijesekeraThilini WijesekeraNicole  P. StephensNicole P. StephensAniket  HingnekarAniket HingnekarHanna  Y. GedamuHanna Y. GedamuNatalie  R. DezsoNatalie R. DezsoMadison  StrangeMadison StrangeNigel  S. AtkinsonNigel S. Atkinson*
  • The University of Texas at Austin, Austin, United States

The final, formatted version of the article will be published soon.

The Drosophila Dif gene uses alternative mRNA processing to encode two different NF-κBs. The DifA isoform is a canonical NF-κB transcription factor that is important for activation of the immune response. Our primary interest is in the DifB isoform which is neuronal specific and is expressed in the mushroom bodies and antennal lobes of the adult brain. The DifB protein lacks a nuclear localization signal, and does not enter the nucleus. Instead, it localizes to the cell body surrounding the nucleus, to axonal-dendritic projections, and to the synapse. DifB is an unusual member of the NFKB superfamily in that it acts outside of the nucleus to modulate behavior. The DifB isoform has been shown to modulate the sensitivity of the adult to sedation by alcohol. Here we conducted a survey to determine whether the DifB NF-κB is important for other fly behaviors. We observed that a DifB-specific mutation strongly suppresses male courtship. However, despite the expression of DifB in the mushroom bodies, a DifB null allele does not interfere with learning in a learned-suppression-of-phototaxis assay. Finally, both DifA-specific and DifB-specific mutations caused flies to have a circadian long rhythm phenotype, albeit the circadian phenotype cannot be scored in male DifB mutants because of a sexually dimorphic locomotor defect.

Keywords: NF-κB, NF kappaB, Courtship, circadian rhythmicity, Learning, synaptic localization, Drosophila melanogaster, Alternative Splicing

Received: 19 Aug 2025; Accepted: 05 Nov 2025.

Copyright: © 2025 Wijesekera, Stephens, Hingnekar, Gedamu, Dezso, Strange and Atkinson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Nigel S. Atkinson, nsatkinson@austin.utexas.edu

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